Electrophysiological mechanisms of J. Pagerols action of ...€¦ · Terapia electroconvulsiva. Hipótesis anticonvulsiva. Electrofisiología. Mecanismo de ac-ción. INTRODUCTION

49 343Actas Esp Psiquiatr 2009;37(6):343-351

Mecanismos de acción electrofisiológicos de laterapia electroconvulsiva

Pese a la elaboración de guías y consensos sobre susindicaciones y aplicación, la terapia electroconvulsiva(TEC) sigue siendo uno de los procedimientos terapéuticoscon menor certeza en su mecanismo de acción. Es intere-sante evaluar la manera en la que los factores que modu-lan la actividad convulsiva pueden ser modificados poresta terapia y su relación con el efecto terapéutico.

El objetivo del presente artículo es revisar, en el con-texto de las teorías neurobiológicas, la bibliografía exis-tente sobre los mecanismos de acción electrofisiológicosde la TEC, principalmente la hipótesis anticonvulsiva. Elmayor conocimiento sobre dichos mecanismos, puedeconseguir una optimización en la práctica asistencial, asícomo un punto de partida para buscar tratamientos alter-nativos basados en las mismas bases físicas.

Entre todos los artículos y libros de texto, se han se-leccionado aquellos trabajos que, por su metodología ydiseño, aportan datos científicamente relevantes respectoal tema principal de esta revisión y que hayan sido pu-blicados entre 1993 y 2007. A fin de aportar mayor con-sistencia al texto, también se han incluido una serie deartículos, previos a 1993, considerados importantes en elámbito que se trata, puesto que establecen las bases teó-ricas de la TEC y han sido citados con frecuencia tras supublicación.

Las evidencias científicas obtenidas se sistematizan entres apartados: conceptos básicos, hipótesis neurofisioló-gicas y hallazgos electrofisiológicos.Palabras clave:Terapia electroconvulsiva. Hipótesis anticonvulsiva. Electrofisiología. Mecanismo de ac-ción.

INTRODUCTIONSince the introduction of electroconvulsive therapy (ECT)

almost 70 years ago, it has been shown to have constant ef-fectiveness in the treatment of depression, mania and schi-zophrenia.1 Knowledge on the limitations of the drug treat-

In spite of the guidelines and consensus on its indicationsand application, electroconvulsive therapy (ECT) continues tobe one of the therapeutic procedures with less knowledge onits mechanism of action. It is interesting to evaluate the wayin which the factors that modulate the convulsant activity canbe modified by this therapy and its relation with the thera-peutic effect.

The aim of the present article is to review, in the contextof neurobiological theories, the bibliography regarding theelectrophysiological mechanisms of action of ECT, mainly theanticonvulsant hypothesis. Having better knowledge aboutthese mechanisms can achieve an improvement in the clinicalpractice and provide a starting point to search for alternativetreatments based on the same physical bases.

After doing a study of all the papers and reference books,those works which, according to their methodology and design,provide relevant scientific information with regard to the prin-cipal topic of this review and that have been published betwe-en 1993 and 2007 were selected. In order to provide better con-sistency to the text, a series of articles prior to 1993 that wereconsidered important within the setting studied have been in-cluded, since they establish the theoretical bases of ECT and ha-ve been frequently mentioned after their publication.

The scientific evidence obtained is systematized into threesections: basic concepts, neurophysiological hypotheses andelectrophysiological findings.Key words: Electroconvulsive therapy. Anticonvulsant hypothesis. Electrophysiology. Mechanism ofaction.

Actas Esp Psiquiatr 2009;37(6):343-351

Reviews

Electrophysiological mechanisms ofaction of electroconvulsive therapy

1 Psychiatry DepartmentCentres Assistencials Emili Mira i LópezSta. Coloma de Gramenet (Barcelona) (Spain)

2 Psychiatry DepartmentBenito Menni. Hospital General de Granollers Granollers (Barcelona) (Spain)

R. Sánchez1

Ò. Alcoverro2

J. Pagerols1

J. E. Rojo2

Correspondence:Roberto Sánchez GonzálezServicio de PsiquiatríaCentres Assistencials Emili Mira i López C/ Prat de la Riba, 17108921 Sta. Coloma de Gramenet(Barcelona) (Spain)E-mail: [email protected]

Electrophysiological mechanisms of action of electroconvulsive therapyR. Sánchez, et al.


ment in the therapeutic approach of the psychiatric disor-ders gave rise to a renewed desire to investigate on ECT,which was initiated in the 1970’s and has continued up todate.

Even though guidelines and consensuses have been ela-borated on its indications and application,2,3 it continues tobe one of the therapeutic procedures with the least cer-tainty in its mechanism of action (up to date, more than100 theories have been proposed4) with great variability inthe opinions regarding its safety and efficacy by the gene-ral population and the health care professionals. On theother hand, it has often been criticized, based on biased in-formation, basically regarding its side effects, principally onthe mnesic level.

Regarding its mechanisms of action, it is interesting toevaluate how the factors that modulate convulsant activitycan be modified by ECT and its relationship with the thera-peutic effect. The anticonvulsant hypothesis has the grea-test support. 5,6

During the treatment cycle, ECT gives rise to an increa-se in the seizure threshold and decrease of the seizure du-ration, so that the magnitude of increase in the seizurethreshold is correlated with clinical response.5,7 This ob-servation supports the anticonvulsant hypothesis,8 thatdefines ECT-induced seizure as an active process in whichsubstances are released into the CNS that decrease brainexcitability, suppress seizure and are essential for the the-rapeutic effect.

Having better knowledge on the ECT mechanism of ac-tion can achieve optimization in the care practice and be astarting point to search for alternative treatments based onthe same physical basis. 9

OBJECTIVE

The purpose of this article is to review, within the con-text of neurobiological theories,10 the electrophysiologicalmechanisms of action of ECT, mainly the anticonvulsanthypothesis.

METHODOLOGY

The bibliographic sources were obtained using two me-thods: 1) Consulting reference textbooks in the field of ECTand the American and Spanish consensuses on the use ofthis therapy. 2) Electronic search for articles in the data ba-ses PUBMED and EMBASE, using different combinations ofthe following terms in English: electroconvulsive, therapy,anticonvulsant, hypothesis, neurobiological, neurophysio-logical, long-term potentiation, electroencephalography,seizure and threshold, as well as a search with the sameterms in Spanish in the database IME.

Among all the results obtained, those works which, dueto their methodology and design contributed scientificallyrelevant data regarding the principal subject of this reviewand that had been published between 1993 and 2007 wereselected. The Jadad scale11 was used for the selection of ori-ginal articles and the Cochrane criteria12 for the review arti-cles. Those articles that did not fulfill the previously descri-bed criteria and/or whose content was not directly relatedwith the purpose were excluded.

In order to provide better consistency to the text, a seriesof articles prior to 1993 that were considered important wi-thin the setting studied have been included, since they es-tablished the theoretical bases of ECT and have been fre-quently mentioned after their publication.

In all, the following were consulted: 7 textbooks, 2 onli-ne documents, 27 original articles and 18 review articles.Nine of these publications were prior to 1993. Even thoughthey met the previously described selection criteria, 8 arti-cles were excluded due to their methodology.

REVIEW

Basic concepts

In this first section, the essential theoretical aspects on whichthe neurophysiological hypotheses are supported and the elec-trophysiological changes related with ECT are presented.

Neuronal physiology during seizures

Nerve signals are transmitted by action potentials, whichare fast changes in membrane potential. In order to con-duct a nerve signal, this potential is moved over the nervefiber until reaching its tip. Each action potential beginswith a sudden change of the normal negative resting po-tential, which is approximately -90 millivolts, to a positivemembrane potential (at the expense of the opening of theion channels and massive sodium entry into the intracellu-lar space). The process ends with a return, almost equallyfast, to the negative potential thanks to a rapid diffusion ofpotassium ions towards the extracellular space. Thus, thethree action potential phases are: resting phase, depolariza-tion phase and repolarization.13,14

The potential change may occur if direct stimulation isapplied with electric current, basically depending on threeparameters: electric current intensity, temporal dynamicsand direction of the current flow. 14

The purpose of electroconvulsive stimulation is to provi-de electrical stimulation with the sufficient potential sothat an elevated percentage of neurons would be dischar-ged at the same time and thus induce adequate seizure. It isinitiated by the massive synchronic recruitment of some in-



tracerebral neuronal sites, such as occurs in the major spon-taneous type motor seizure.1 Due to the complex structuraland electrophysical properties of the skull and brain, elec-trical stimulation during ECT requires much higher doses ofcurrent than those used to stimulate the nerve fibers ornerve tissues under experimental conditions.14

Adequate seizure and intensity of the stimulus

In the recommendations for treatment with ECT, it isconsidered that if an adequate generalized seizure is indu-ced in each session (a seizure lasting between 15 and 20 se-conds on the electroencephalographic level is currently ac-cepted2), the patient has received an optimal and effectivetreatment.

A subconvulsive electrical stimulus is that which is notable to induce seizure, while an aborted or short seizure isthat whose duration is less than that mentioned. Age, in-itial seizure threshold, absolute doses of anesthetics, andnumber of previous ECT sessions are the principal factors in-versely related with seizure time.7,9

At present, it is stated that the duration by itself is notsufficient to establish whether a seizure has been adequate,the electroencephalographic characteristics of it becomingincreasingly important (recruitment phase, typical spike-and-wave complexes and post-ictal suppression). Thus, du-ration is incomplete as a measure of the convulsant activity,since it does not express the intensity, uniformity or its dis-tribution through the brain.15,16

Seizure threshold

It is defined as the smallest amount of electrical energyneeded to induce an adequate seizure.9 This parameter is in-fluenced by all those factors that may affect electrical im-pedance and neuronal excitability.

Many studies have related the increase of the seizurethreshold with clinical response to ECT. As a general rule,this increase generally has a range of 40 to 100% during thecourse of the therapy. In two different clinical trials (1987and 1993)17,18 with a total of 145 patients, the Sackeimgroup demonstrated that the percentage of increase in theseizure threshold is greater in the group of patients that canbe considered responders to ECT than in the group of pa-tients with limited response.7 It should be taken into ac-count that this parameter is affected by all of the variablesmentioned in the following and that are summarized in ta-ble 1:

– Age and gender.– Location of the electrodes: bilateral bifrontotemporal pla-

cement has a greater seizure threshold than the right unila-teral one proposed by D’Elia. A total of 40% of the patients

have a seizure threshold under 50 mC when right unilateralECT is applied, while this percentage decreases to 7% whenbilateral ECT is applied. The cause of this is not clear but itmay be because in the unilateral ECT, the current passesthrough the brain structures with lower seizure thresholds.In spite of this, the application of right unilateral ECT requi-res higher doses to be effective.7,9,19,20

– Anesthetic agents: an excessive dose of this group ofdrugs produces short and aborted seizures, prolongspost-ictal recovery, increases the risk of anesthetic com-plications and intensifies amnesic effects. 21,22 The in-fluence of methohexital and propofol in convulsive acti-vity and in the recovery profiles were analyzed byFredman at al. (1994) in a cross-sectional randomizedstudy.23 Although the use of propofol was associated withshorter seizure durations on both the motor and electro-encephalographic levels, in comparison with methohexi-tal, this difference was not clinically significant since thedurations exceeded 30 seconds in both groups.

– Psychotropic drugs: in general, no systemic research studiesin humans have been done. Most of the information comesfrom research in animals and clinical experience. 9,20,22

– Sleep deprivation: Gilabert et al. (2004)24 observed thatsleep deprivation during treatment with ECT produces adecrease in the seizure threshold (from 190.4 mC in thefirst session to 176.4 mC in the last one) in regards tothose patients who were not sleep deprived (in these,they found an increase in the threshold from 190.4 mC to321.91 mC). In this context, they question whether theprogressive increase of the threshold is the cause of theefficacy.

Parameter Seizure Observationsthreshold

Table 1 Factors that affect the seizurethreshold7,9,19-22,24

Age

Gender

Electrode position

AnestheticsDrugs

Sleep deprivation

Loss of cerebral plasticity in theelderly

Men (greater cranial thickness andneuronal mass)

WomenBL ECTRU ECTPropofol > methohexitalBenzodiazepines and anticonvulsantsAdenosine antagonists (caffeine and

theophylline), lithium carbonate,neuroleptics and clozapine

↑

↑

↓↑↓↑↑↓

↓

↑: increase; ↓: decrease; TBL ECT: bilateral ECT; RU ECT: right unilate-ral ECT.



Neurophysiological hypotheses

The two main neurobiological hypotheses of the mecha-nism of action of the antidepressant effect of ECT are anti-convulsant hypothesis and the seizure generalization hypo-thesis; the hypothesis of diencephalic stimulation hasevolved towards a subtype of the latter.25 Both hypothesesare described in the next section, together with the pre-frontal model and anatomico-ictal theory.

Anticonvulsant hypothesis

Seizure is necessary for efficacy of the ECT, however, it isnot sufficient to explain it. Thus, the events that occur du-ring and after the seizure must be taken into account. Thisis why the hypothesis was proposed that seizure provoca-tion precipitates a self-limited endogenous process.26,27 Sei-zures do not end due to an inadequate supply of carbohy-drates or neuronal exhaustion, or due to other passiveprocesses (epileptic status indicates that the brain is able ofmaintaining the convulsive activity for days). The termina-tion of the episode is an active inhibitory process essentialfor the efficacy of ECT. 28,29

As we have already seen, it has been established that ECThas potent anticonvulsant properties, 7,17,18,30 as demonstratedby 1) the progressive increase of the seizure threshold and de-crease of the seizure duration, that we would designate as atolerance phenomenon during the treatment with ECT; 2) theregional and/or global reductions of the cerebral blood flowand cerebral metabolic index; 3) the induction of a slow waveactivity in the electroencephalogram (EEG) and 4) the increaseof the functional activity of the neuropeptides and neuro-transmitter inhibitors that occurs with the ECT. 7,9,31

These findings have been principally described by Sackeimet al. in different studies conducted in the 1980’s and 1990’s.However, there has not been any independent confirmation ofthese results. Subsequent investigations have not been able toconclude that the absolute value of the threshold or the mag-nitude of its increase during a course of ECT is useful to pre-dict clinical outcome. On the contrary, most of the studiesshow the opposite relationship: the greater the increase of theseizure threshold, the worse the clinical response. In spite ofthis, only isolation and identification of an endogenous anti-convulsant substance (specifically associated with ECT-indu-ced seizures in humans) followed by the demonstration thatits blockade does not influence clinical improvement, couldinvalidate the anticonvulsant hypothesis. 25

Seizure generalization hypothesis

This hypothesis is different from the others regarding theECT mechanism of action because it does not invoke neuro-chemical mechanisms but rather neurophysiological ones.It proposes that the more extensive (and in some way more

efficient) the ECT-induced brain seizure activity is, the bet-ter the antidepressant clinical response will be. The hypo-thetical construct of seizure generalization integrates seve-ral findings regarding the complex relationships betweenthe technical aspects of the ECT administration and thera-peutic impact.25

Sackeim et al. (1996) found that the greater antidepres-sant activity of the ECT was associated to an increase of theinter-ictal suppression in the anterior prefrontal regions.32

Along these same lines, previous findings related the reduc-tion of cerebral blood flow induced by ECT (in the sameanatomical areas) with clinical response. 33 The reduction ofthe regional glucose metabolism produced in the frontal lo-bes after the application of bitemporal ECT also agrees withthese results.34-36

The electroencephalographic findings related with thishypothesis will be described further on.

The diencephalic hypothesis of ECT is currently includedwithin the seizure generalization hypothesis, as a specialform of it. It postulates that for the complete developmentof the therapeutic effect of the ECT, the seizures inducedshould be sufficiently generalized to include those dience-phalic centers involved in the regulation and modulation ofthe appetitive behaviors, daytime rhythms, hormone releaseand physiological homeostasis.25 The most easily demons-trable prediction of this hypothesis is that the ECT-inducedseizures that are not associated to tachycardia reflect gooddevelopment and a peak in the cardiac output rate (resultof the stimulation of the cardioaccelerator center on thediencephalic level) will be translated into a limited antide-pressant clinical response. 37-39

Although the seizure generalization hypothesis in ECT isbased on a powerful combination of ictal and inter-ictalevents, its confirmation requires the demonstration thatthese mechanisms are necessary requirements for the im-provement in the depressive systems to take place after theapplication of the ECT. 25

Prefrontal model

On the bases of the differences existing in regards to do-se and efficacy when unilateral and bilateral ECT are com-pared, the importance of the spatial distribution of the lowdensity and the initiation of the resulting seizure activityhas been proposed. While the unilateral ECT concentratesthe low density in the anterior two thirds of the hemispherestimulated, the bilateral one concentrates the effects in theprefrontal regions.25

The magnitude of the reductions in the cerebral bloodflow (CBF) in the specific prefrontal regions is related withthe efficacy of ECT, and the responders to this therapy havemore likelihood of post-ictal suppression and of developing



slow wave activity on the EEG than the nonresponders.Thanks to the improvement of the techniques, the possibi-lity of identifying specific functional networks associated toefficacy has increased.40

It has been postulated that the right unilateral ECT at highdoses implies significant reductions of the CBF in the anteriorprefrontal cortex. Bilateral ECT is characterized by a markedanteroposterior gradient, concentrated near the prefrontalpole where it is more likely that the seizures are initiated. The-se observations are important to clarify the critical brain re-gions for the treatment efficacy and to understand the dose-response ratio of the electrical stimulation.34-36,40

The prefrontal model is the simplest and most pragmaticof those previously described, so that some of the clinicalcharacteristics associated to the response, that require morecomplex models (for example of the relationship betweenthe post-ictal suppression in the EEG and the clinical impro-vement with ECT) cannot be explained with it. Combiningthe different models makes it possible to give more mea-ning to the neurophysiological hypotheses, since these re-present different phases of the ECT-induced seizures: theprefrontal model specifies the critical anatomical regionsfor the initiation of the seizure and the generalization mo-del specifies the different characteristics of the expansionof the episode and the diencephalic participation.25

Anatomico-ictal theory

The anatomico-ictal theory is a unification of the neu-rophysiological hypotheses of ECT. Its heuristic value gives itmore possibilities of being correct then the individual com-ponents separately.

It postulates that the seizure episodes precipitated byECT will have a better antidepressant clinical effect if theyare initiated in the prefrontal regions of the brain and wi-dely extend towards the cortex and subcortex, involving thediencephalic centers. 25

Electrophysiological findings

In this section, the electroencephalographic changes thatoccur, the mechanisms involved in the termination of theseizure and, finally, some aspects related with the long-termpotentiation and neurogenesis are described.

Electroencephalographic changes

1. Ictal Electroencephalogram

During treatment with ECT, we can observe some typicalelectroencephalographic phases (see Figure 1): 1,41

– Baseline. The baseline EEG before the stimulus can besignificantly different from the baseline EEG of an awa-ke patient, due to the anesthetics administered. It oftenconsists in a mixture of fast and slow activity that mayhave greater amplitude than that observed while awa-ke. The effect varies depending on the depth of anes-thesia.

– Electrical stimulation. During this period, the EEG activityis blocked by interference of the stimulus current.

– Pre-ictal stimulation. After electrical stimulus, a shortpre-ictal period of low amplitude fast activity can some-times be observed.

– Epilepsy recruitment rhythm. It is a brief period of veryrhythmic activity, of low to moderate alpha or beta am-plitude, that appears after the pre-ictal activity. It is be-lieved that this phenomenon is associated to thesynchronizing effects of the thalamocortical projectionsduring the early phases of the seizure generalization.

– Polyspike activity. The earliest phase that can be observedin the seizure is frequently characterized by a high fre-quency polyspike activity. This phase coincides with theearly tonic and clonic components of the motor responseand generally lasts from 10 to 15 seconds.

– Slow waves and polyspike complexes. During the clonicphase of the ictal motor response, the polyspikes activityevolves to repetitive slow waves and polyspike complexes,that are synchronic with the clonic movements and thatdecrease in frequency as the clonic phase progresses.

– Termination phase (post-ictal suppression). Amplitudeand regularity of the polyspike and slow waves patterngradually decrease. In some cases, the polyspikes andslow waves can terminate suddenly.

– Post-ictal phase. It begins immediately after the termina-tion of the seizure on the EEG, producing a slow increasein amplitude and in frequency, and thus, an approach tothe preanesthetic baseline.

2. Inter-ictal electroencephalogram

ECT gives rise to global and topographic changes in thefunctional activity of the brain. During the post-ictal pe-riod, a considerable amount of slow wave activity (delta andtheta) is produced that reflects the spatial extension of theneuron populations subject to inhibition.42,43 That is whythe inter-ictal EEG tends to become slower and has greateramplitude with the administration of successive sessions ofECT, returning to normality 1 to 12 months after treatmenttermination. Acetylcholine is involved in the developmentof these electroencephalographic changes, which are a signthat the seizures and persistence of their effects have beenproduced.44,45

Sackeim et al. (1996),32 in a randomized study for diffe-rent conditions of the application of ECT to 62 patients withmajor depressive disorder, concluded that induction of slowwave activity in the cortex is associated with the ECT effi-cacy. They emphasized the anteroposterior gradient and the



Figura 1 Electroencephalographic recordings of different phases of the typical convulsion of the ECT. EEG: electroence-phalogram; EMG: electromyogram; ECG: electrocardiogram; R: recruitment phase. The asterisks are artifacts inthe recording provoked by the movement. Source: own production.

BASELINE RECORDINGS STIMULATION

POLYSPIKES POLYSPIKES AND SLOW WAYES

POLYSPIKES AND SLOW WAVES

FINALIZATION (POST-ICTAL SUPPRESSION)



fact that both the reduction of the cerebral blood flow(CBF) in the prefrontal cortex and the increase of the deltaactivity are related with clinical efficacy.

There are other important findings described by differentresearch groups:7,9,46 post-ictal suppression is deeper withbilateral ECT than with unilateral; seizures with bilateral ECThave greater ictal EEG amplitude, symmetry, coherence,morphological regularity and post-ictal suppression thanwith unilateral ECT; the increase of the electrical dose andbilateral position of the electrodes correlates both positivelywith greater voltage and regularity of the ictal EEG andgreater post-ictal suppression of the EEG activity is associa-ted to a more positive treatment outcome.

Mechanisms of seizure termination

The mechanisms involved in the seizure episode termina-tion have been described based on studies on epilepsy andin experimental animals. Those having the greatest impor-tance involve the potassium channels, zinc and the gabaer-gic system.

– ATP dependent potassium channels (KATP). They are ex-pressed on the pre- and post-synaptic level in many brainregions. Their function is controlled by the metabolicstatus of the neuron. A decrease in the ATP:ADP ratio ac-tivates these channels, limiting the cellular excitabilityand release of transmitters during the metabolite stressphases. Recent studies show the importance of the KATPin the control of neuron excitability, propagation of theseizure and control of seizure threshold.47

– Potassium channels activated by G. proteins. Their activa-tion represents an important mechanism by which theneurotransmitters and neuropeptides regulate the neuronexcitability. They are located on the pre-and postsynap-tic level and their activation reduces the release of trans-mitters and the response to this synaptic inputs. 47

– Gamma-aminobutyric acid (GABA). It is the main inhibi-tory neurotransmitter in the brain. Because multiple ex-periments have demonstrated that the gabaergic neuro-transmission blocker substances generate seizures in thecontrol tissues and that different gabaergic system po-tentiators have antepileptic actions in human patients, ithas been suggested that gabaergic activity prevents theseizures. In the same way, it has also been widely obser-ved that activation of the glutamatergic synapses gene-rates seizures. 48,49 It is postulated that the neural hypo-metabolic state that follows the ECT is associated andperhaps is produced by an increase in the gabaergictransmission.26

– Zinc. It is concentrated in certain excitatory pathways ofthe CNS, especially in the mossy fibers of the hippocam-pus, where it has been suggested that it modulates trans-mission and synaptic plasticity. Bancila et al. (2004),using rat mossy fiber synaptosomesm, applied zinc in mi-crosomal concentrations during a short anoxic-hypogly-

cemic episode. They found that through the activation ofthe presynaptic KATP channels, zinc protects the neuronsagainst hyperexcitation, excessive release of transmittersand excitotoxicity. They postulated that zinc probablyacts as an endogenous neuroprotector during pathologi-cal conditions such as epilepsy or stroke.50

Changes in synaptic plasticity and long term potentiation

In recent years, many investigations on neurobiology ofthe memory have focused on the electrophysiological phe-nomenon known as long-term potentiation (LTP). This is anexperimentally induced form of synaptic plasticity, easilydemonstrable in the hippocampus, that constitutes a lastingincrease of the excitatory synaptic force. It has been propo-sed as a plausible mechanism of the neural substrate of le-arning. Several experiments have demonstrated that the re-peated application of electroconvulsive stimulation (ECS) inrats produces a marked block of the LTP in the hippocampusand neocortex.51,52 This mechanism has been proposed asthe possible causing factor of cognitive and mnesic condi-tions that appear after an ECT cycle.53

On the other hand, it has been postulated that the bene-ficial effect of ECT in the treatment of acute depressive di-sorders54 may be related with changes in synaptic plasticityand blockade of the long term depression processes (LTD) onthe striatal level.55

DISCUSSION AND CONCLUSIONS

There are several aspects that limit the empirical validityof the electrophysiological mechanisms of action, both the-oretical and methodological. The substantial increase of theseizure threshold is a necessary, but not sufficient, condi-tion for response to ECT. Patients in whom the physiopatho-logy of the disorder is not related with the excessive disin-hibition or excitation may not respond to treatment.9 As hasalready been seen, during the course of the treatment, a se-ries of dynamic changes occur. The accumulated anticon-vulsant effect may directly affect the expression of a seizu-re, independently of the effects produced by the intensityof the electrical stimulus.7

After reviewing the literature on the electrophysiologicalmechanisms of action of electroconvulsive therapy, we candraw the following general conclusions: 1) There are datathat support electrophysiological changes, but the differentneurobiological series cannot be contemplated indepen-dently due to the complexity of the brain function thatinvolves the interaction of biochemical, hormonal and elec-trophysiological systems. 2) ECT has anticonvulsant proper-ties, the termination of the episode needing an active andessential inhibitory process for its efficacy, bringing about acomplete series of neuronal mechanisms. 3) The seizurethreshold is a filter for many of the neurobiological effects



Electrophysiological mechanisms of action of electroconvulsive therapy

of the electrical stimulus and consistent relationships existbetween the electrical dose and the behavioral effects onlyafter it has been exceeded.9 4) It is postulated that the LTPblockage that appears after the electroconvulsive stimula-tion can be the underlying mechanism to the cognitive andmnesic alterations that appear after the application of ECT.5) The many findings published on ECT and electroconvulsi-ve stimulation should be replicated to be able to differen-tiate the effects that are primary from those that are secon-dary and discover which are really therapeutic. 6) Moreexperiments are needed to increase or block the anticonvul-sant properties of ECT and determine the effects that areproduced in its efficacy.7 7) Having better knowledge of themechanisms of action will make it possible to develop othermore effective techniques based on them.

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Electrophysiological mechanisms of J. Pagerols action of ...€¦ · Terapia electroconvulsiva. Hipótesis anticonvulsiva. Electrofisiología. Mecanismo de ac-ción. INTRODUCTION